Obesity, an extremely common and detrimental metabolic disease, poses serious threats to the public health both in the US and worldwide. The prevalence of this disorder has markedly increased since the mid-1980s. In the United States, 50% of adults are overweight and 30% are obese. Even more seriously, the prevalence of obesity and associated diabetes are increasing rapidly in children. The impact of obesity on the individual, the family, and society, especially with respect to the cost and utilization of health care resources, is very serious. Therefore, controlling body weight is not just a scientific topic but also a matter of growing social concern.
Mast cells (MCs) help induce an allergic response by releasing cytoplasmic granules, whose contents promote allergic inflammation upon sensitization by IgE or complement factors (Schwartz, et al., Prog. Allergy 34:271-321 (1984); Mekori, et al., J. Allergy Clin. Immunol. 104:517-523 (1999)). Recent biochemical and histological observations suggest that MCs may also participate in blood-borne leukocyte recruitment (Mekori, et al., J. Allergy Clin. Immunol. 104:517-523 (1999)), smooth muscle cell (SMC)/endothelial cell (EC) proliferation (Toda, N., Circ. Res. 61:280-286 (1987); Inoue, et al., Am. J. Pathol. 149:2037-2054 (1996); Mueller, et al., Circ. Res. 77:54-63 (1995)), apoptosis (Latti, et al., J. Cell. Physiol. 195:130-138 (2003); Leskinen, et al., Arterioscler. Thromb. Vasc. Biol. 23:238-2343 (2003); Leskinen, et al., Biochem. Pharmacol. 66:1493-1498 (2003)), T-lymphocyte migration and activation (Mekori, et al., J. Allergy Clin. Immunol. 104:517-23 (1999)), angiogenesis (Zudaire et al., Am. J. Pathol. 168:280-291 (2006)), and matrix remodeling (Daugherty, et al., Curr. Atheroscler. Rep. 4:222-227 (2002)). To date, a clear role for mast cells with respect to obesity has not been determined.
The discovery of mast cell-null mice (Duttlinger, et al., Proc. Natl. Acad. Sci. USA 92:3754-3758 (1995); Wolters, et al., Clin. Exp Allergy 35:82-88 (2005)) and the availability of obesity models (both genetic and diet-induced obese mice) have now made it possible to assess the role of mast cells in obesity and its complications. In addition, the availability of gene knockout mice for important mast cell mediators or white adipose tissue (WAT) chemokine receptors makes it possible to identify the mediators in mast cells that are essential for obesity and the chemokines in WAT that are required for mast cell homing.